The extracellular matrices of bones and teeth that give these unique tissues their shape and strength are synthesized and maintained throughout life by highly specialized cells. The cells' ability to assemble, mineralize and maintain the matrices is generally thought to be modulated through a variety of noncollagenous proteins (NCP). The goal of this project is to study the structure and function of several of these noncollagenous proteins. We have completed the cloning and sequencing of human and certain useful animal model noncollagenous proteins including bone sialoprotein (BSP), osteopontin (OPN), decorin (DCN), and biglycan (BGN). The human biglycan gene has been sequenced and localized to the end of the long arm of the X chromosome. Comparison of the BGN gene structure to other TGF-~ binding proteins has led us to hypothesize that the TGF-~ binding domain may be in the C-terminal disulfide loop. The human decorin gene has been partially cloned and is much larger than BGN. Its intron-exon junctions, however, appear to be identical to the BGN gene. The DCN gene is located at 12q21.3. We have successfully produced monospecific antisera to all of the major NCP. In collaboration with Dr. Paolo Bianco, we have used both the antisera and cDNA probes to begin studies on the developmental pattern of expression of these proteins in human and rodent models. Production of the mg quantities of nondenatured protein necessary for structure-function studies has been successful for rat BSP. We have conducted physicochemical studies on the purified BSP. Furthermore, we have preliminary evidence for a cryptic cell attachment domain other that the ArgGlyAsp (RGD) tripeptide typical of the integrin-binding class of receptors.